Determination of finasteride in human plasma by liquid chromatography–electrospray ionization tandem mass spectrometry with flow rate gradient
School of Pharmacy, Nanjing Medical University, Nanjing, 210029, People's Republic of China.European Journal of Drug Metabolism and Pharmacokinetics (Impact Factor: 1.56). 01/2011; 35(3-4):137-46. DOI: 10.1007/s13318-010-0013-x
In this study, an attempt was made to describe and validate liquid chromatography-electrospray ionization tandem mass spectrometry as a fast, sensitive and reproducible method for determining finasteride in human plasma. Finasteride and internal standard (pantoprazole) were extracted by liquid-liquid extraction using methyl tert-butyl ether. Separation was performed by using a flow rate gradient on a reverse phase C18 column at 25°C. The mobile phase consisted of methanol-water (70:30, v/v) containing 0.5% anhydrous formic acid. The protonated analytes were quantitated in positive ionization by multiple reaction monitoring in mass spectrometry. The mass transitions are m/z 373.4→305.3 and 384.1→200.0 for finasteride and pantoprazole, respectively. The method had a run time of 3.6 min and a linear calibration curve at a range of 0.2-100 ng mL(-1) (r2=0.9958). The lower limit of quantification was 0.2 ng mL(-1). The extraction recoveries of finasteride from the biological matrix were more than 82.7%, and the intra- and inter-day precision of the assay at four concentrations were 2.4-8.0% with an accuracy of 94.3-105.8%. The developed method requires less plasma (0.1 mL), but has high sensitivity. The validated method has been successfully used to analyze human plasma samples in pharmacokinetic or bioequivalence studies.
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ABSTRACT: A specific, fast and sensitive LC-MS/MS assay was developed for the determination of finasteride in human plasma using betamethsone dipropionate as the internal standard (IS). The limit of quantification was 1.0 ng/ml and the method was linear in the range of 1.0-25.0 ng/ml. The retention times were 0.75 min for finasteride and 0.85 min for IS. Method intra-batch precision and accuracy ranged from 3.6 to 7.1%, and 96.6 to 103.9%, respectively. Inter-batch precision ranged from 2.5 to 3.4%, while Inter-batch accuracy ranged from 100.3 to 103.5%.The analytical method was applied to evaluate the pharmacokinetic and relative bioavailability of 2 different pharmaceutical formulations containing 1.0 mg of finasteride. This study evaluated 38 volunteers in a randomized, 2-period crossover study with 7 days washout period between doses. The geometric mean and respective 90% CI of finasteride test/reference percent ratios were 95.68% (91.2 - 104.6%) for Cmax, 97.5% (92.1 -103.3%) for AUC0-t and 98.1 (92.67-103.8) for AUC0-inf. Based on the 90% confidence interval of the individual ratios (test formulation/reference formulation) for Cmax and AUC0-inf, it was concluded that the test formulation is bioequivalent to the reference one with respect to the rate and extent of absorption of finasteride. © Georg Thieme Verlag KG Stuttgart · New York.04/2015; 65(9). DOI:10.1055/s-0034-1376962
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